SP110 as a novel susceptibility gene for Mycobacterium avium subspecies paratuberculosis infection in cattle.

The intracellular pathogen resistance 1 (Ipr1) gene has been reported to play a role in mediating innate immunity in a mouse model of Mycobacterium tuberculosis infection, and polymorphisms of its human ortholog, SP110 nuclear body protein, have been suggested to be associated with tuberculosis. Thus, the bovine SP110 gene was considered to be a promising candidate for a genetic association study of bovine paratuberculosis, or Johne's disease, a chronic granulomatous enteritis caused by Mycobacterium avium ssp. paratuberculosis (MAP). Initially, single nucleotide polymorphisms (SNP) within the bovine SP110 gene were identified, and subsequently a population-based genetic association study was carried out. Seventeen new SNP along the SP110 gene were identified in Holstein-Friesian cattle, and 6 more were compiled from public databases. A total of 14 SNP were included in the association study of 2 independent populations. The SNP c.587A>G was found to be significantly associated with MAP infection, with the major allele A appearing to confer greater disease susceptibility in one of the analyzed populations. In addition, 2 haplotypes containing this SNP were also found to be associated with infection in the same population. The SNP c.587A>G is a nonsynonymous mutation that causes an amino acid change in codon 196 from asparagine to serine. In silico analyses point to SNP c.587A>G as a putative causal variant for susceptibility to MAP infection. The elucidation of the precise mechanism by which this SNP can exert its effect in the protein and, as a result, in the risk of infection, requires future functional analyses. Likewise, the absence of genetic association in one of the analyzed populations renders it necessary to carry out this study in other independent populations, with the aim of substantiating the repeatability of the present results. Nevertheless, the present results deepen our understanding of the genetic basis of susceptibility and resistance mechanisms related to MAP infection in cattle and, in turn, constitute a step forward toward the implementation of marker-assisted selection in breeding programs aimed at controlling paratuberculosis.

[ECMO: experience in paediatrics]. / ECMO: experiencia en edad pediátrica.

INTRODUCTION: ECMO (Extracorporeal Membrane Oxygenation) provides a vital support to patients with supposed reversible respiratory and/or cardiac failure, in whom conventional support techniques have been previously unsuccessful. OBJECTIVES: To determinate the criteria used in our hospital to put paediatric patients on ECMO, compare their clinical course depending on their pathology (respiratory failure, congenital heart disease or sepsis) and identify the sequelae attributable to this technique. MATERIAL AND METHOD: A retrospective review of clinical records of all patients on ECMO support in our centre, excluding those presenting typically in neonatal period. RESULTS: ECMO was used on 16 patients from June 2001 to January 2007, of which 50% were males. The median age was 7 months (from 21 days to 11 years). The reason for starting ECMO was respiratory failure in 11 cases (oxygenation index >40 and/or alveolar-arterial oxygen gradient >605), congenital heart disease in 2 and sepsis in 3 (due to shock unresponsive to adequate resuscitation). The median time to starting ECMO from PICU admission was 3.58 days (from 12h to 9 days). Venovenous cannulation was used initially in 8 patients, but 5 of them needed venoarterial ECMO later. The technique was used for a mean of 8 days (from 1 to 28 days). The main complication was the isolation of bacteria in different cultures (8 patients). The overall survival was 50% (6 patients with respiratory failure and both patients submitted to cardiac surgery). Extracorporeal support was withdrawn in 7 children because their clinical situation was irreversible. Another patient died seven days after successful decannulation. We have not found any serious sequel among survivors that could be attributable to this technique. CONCLUSIONS: Survival among children supported with ECMO in our hospital is similar to that recorded by the ELSO in 2004, although the prognosis depends on the initial pathology. There are different criteria for starting this technique depending on the underlying diseases: respiratory index of poor prognosis in patients with respiratory failure, haemodynamic instability in those with sepsis or cardiac failure after cardiovascular surgery. We have not found any serious sequel among the survivors which could be attributable to this technique.

[Nutritional and surgical management of short bowel syndrome. Our last 6 patients' experience]. / Manejo nutricional y quirúirgico del intestino corto como causa de fracaso intestinal en niños. A propósito de seis pacientes.

BACKGROUND: Children cause of intestinal failure is short-bowel syndrome. It provokes an altered absorption of nutrients and makes patients to be dependent on parenteral nutrition (PN) while they wait or not for an intestinal transplantation, with its side effects. It is crucial to achieve the maximum efficiency of remaining intestine. Many surgical techniques have been led to reduce stasis of dilated small intestine and improve the mucosal surface area for absorption. METHODS: Six patients have presented intestinal failure because of a surgical resection during newborn period. 2 gastroschisis, 2 intestinal atresias (Apple-peel), 1 necrotizing enterocolitis (NEC) and 1 midgut volvulus. 4 preserve ileocecal valve (ICV): 2 Apple-peel, 1 NEC and the midgut volvulus. The shortest length of bowel after resection were 12cm without ICV (gastroschisis) and 18cm with ICV in a preterm newborn of 24 weeks of gestational age (midgut volvulus). Tapering and plication have been done in Apple-peel cases. No complementary surgical techniques have been necessary in NEC and volvulus. Gastroschisis cases had 12 and 40 cm of small bowel without ICV. In the first one, during newborn period an intestinal lengthening according to Bianchi was done, followed by sequential transversal enteroplasty (STEP), partial gastrectomy and plication of 1st and 2nd duodenal portion. In the second, an STEP was done. All patients have received cycled and optimized PN (COPN) in our centre, only one case (gastroschisis) proceeding from another centre had received standard PN and developed a great hepatic affectation. RESULTS: 2 Apple-peel have been adapted to normal enteral nutrition after 3 and 18 months of COPN, such as NEC and volvulus (3-6 months). One gastroschisis (12cm) has a normal hepatic function with free oral nutrition and home COPN at 23 months. The other one (40cm) has COPN and started enteral nutrition 1 month after surgery, although its hepatic function remains altered. CONCLUSIONS: Parenteral nutrition is essential for these patients to survive. We would like to enhance the importance of COPN in order to preserve hepatic function. Surgical procedures aim to avoid stasis and bacterial overgrowth and improve intestinal motility. Different techniques may be used alone or sequentially. The purpose of this management is to achieve nutritional autonomy or increase waiting time before intestinal transplantation.

Clinical and immunological spectrum of partial DiGeorge syndrome.

We present four cases of DiGeorge syndrome diagnosed at our center. Onset occurred during the neonatal period and was associated with severe congenital heart disease. In case 1, the patient had heart disease and absence of thymus. Total T-lymphocytes were 34%; total T4-lymphocytes were 27%. Stimulation test with phytohemagglutinin (PHA), concanavalin A (conA) and pokeweed mitogen were negative. Microdeletion was found in the chromosome 22q11 region. The second case involved heart disease, microstomia, round and rotated ears and branchial cyst. Total T-lymphocytes were 38% and total T4-lymphocytes 27%. Thymus was absent. Microdeletion in the chromosome 22q11 region. Case 3 showed heart disease, renal malformation, absence of thymus and parathyroid gland. The patient died 5 days postsurgery. Microdeletion was seen at chromosome 22q11. In the fourth case there was heart disease, microretrognathia, hypertelorism, short neck, absence of thymus and parathyroid glands. Total T-lymphocytes were 22%, total T4-lymphocytes 15%, and total T lymphocytes for pokeweed mitogen were negative. Microdeletion was found at chromosome 22q11. At the age of 13 days the patient died. The cases were recorded during a 2-year period, between 1997 and 1998. The prevalence of DiGeorge syndrome in the number of admissions for congenital heart disease among the neonates at our hospital was 3.14%. Presentation in the form of repeated infections is rare, since most cases of DiGeorge syndrome are partial, and functional cellular immunity is preserved.

[Perinatal intracranial hemorrhage due to immune thrombocytopenia]. / Hemorragia intracraneal perinatal por trombocitopenia inmune.

INTRODUCTION: Immune neonatal thrombocytopenia is caused by maternal antibodies (IgG) passing across the placenta, with subsequent destruction of foetal platelets. There are two forms, the iso-aloimmune forms, with an incidence of intracranial hemorrhage (ICH) in the neonatal period of 10-20%, and the autoimmune form with an incidence of only 1%. OBJECTIVE: To review the patients with this condition in a neonatal unit. CLINICAL CASES: During the past 12 years, three patients with ICH due to immune thrombocytopenia were attended in the neonatal unit. Three newborn babies had ICH (two intrauterine, at 30 and 33 weeks of gestation, and one postnatal) secondary to immune thrombocytopenia (two aloimmune and one autoimmune). Two births were by caesarean section and one was vaginal. All three had thrombocytopenia at birth (12,000; 23,000 and 56,000 platelets/mm3). Immunological study of the platelets from the patients with aloimmune thrombocytopenia showed the absence of HPA-1a in their mothers. The patients were treated with gammaglobulins and platelets. Intracranial hemorrhage was confirmed on neuroimaging in all cases. A porencephalic cyst was seen to have formed in two cases. The clinical course was satisfactory in two patients. However, the third patient had severe motor impairment and died 9 months later. In all three patients the PEV were altered and two had reduced visual acuity. CONCLUSIONS: 1. Perinatal ICH due to immune thrombocytopenia is uncommon, but potentially serious. 2. We suggest that cranial ecographic studies should be done in all newborn babies with immune thrombocytopenia even when no neurological disorder is seen. 3. Early diagnosis and suitable treatment may help to reduce the neurological sequelae. 4. The neurological complications are due to intraparenchymatous hemorrhage, and visual sequelae are frequent.

A composite skin substitute (graftskin) for surgical wounds. A clinical experience.

BACKGROUND: Bioengineered skin substitutes offer tissue replacement without requiring a donor site and might produce better healing. OBJECTIVE: To evaluate the recipient's response to grafting a bioengineered skin equivalent onto acute surgical wounds. METHODS: Graftskin, which is made of: 1) a bovine collagen matrix containing human fibroblasts, and 2) an overlying sheet of stratified human epithelium, was grafted onto the excision sites of 15 patients. RESULTS: Blood and cell studies for toxicity were negative. Graftskin proved easy to handle, and a typical clinical appearance of the skin substitute during "take" was detected. Compared with expectations improved healing occurred. Twelve of 15 patients had initial clinical takes. CONCLUSION: Graftskin was not clinically rejected and was not toxic. It often appeared to take and produced better than expected healing.

Photoelastic models of wound closure stress.

BACKGROUND: Areas of high stress in surgical closures are known to have adverse effects on wound healing. OBJECTIVE: To create a surgical model that will predict areas of high stress and allow for quantitative comparison of stress distributions in different closure geometries. METHODS: Surgical models were constructed consisting of soft polyurethane plastic. Surgical defects corresponding to A to T and O to T closures were cut in the plastic and then closed with silk interrupted sutures. The models were transilluminated with polarized light, photographed, and compared. RESULTS: The A to T closure showed much less total stress than the O to T closure. The color-coded stress patterns indicate that each closure has its own distinct stress characteristics. CONCLUSION: Photoelastic surgical models allow rapid and easy comparison of stress concentrations in different closure geometries. Such detailed information may allow the surgeon to avoid the adverse consequences of stress.

Radiohumeral synostosis, femoral bowing, other skeletal anomalies and anal atresia, a variant example of Antley-Bixler syndrome?

We report a newborn with radiohumeral synostosis, femoral bowing, anal atresia, a prominent nose (pear shaped nose), slender ribs, long tapering fingers with distal camptodactyly, genital hypoplasia and a neonatal humeral fracture. Among the possible differential diagnoses a variant example of Antley-Bixler syndrome is considered to be the most likely final diagnosis.

Zinc chloride paste for the debridement of chronic leg ulcers.

Chronic leg ulcers present a difficult therapeutic problem, and their management requires frequent debridement. Thorough debridement of painful or extensive ulcerations is not always possible. Frequently, it must be done in the operating room, a situation accompanied by the potential complications of general anesthesia and by considerable expense. We present evidence for the effectiveness of zinc chloride paste as a relatively painless debriding agent in the management of chronic leg ulcers. When applied to the wound bed, zinc chloride paste fixes the tissue and leads to the formation of an eschar that falls off within a few days, leaving a granulating ulcer suitable for grafting.

Micrographic surgery for the microscopically controlled excision of carcinoma of the external ear.

Micrographic surgery is particularly valuable for treating carcinomas of the external ear because the total microscopic control of excision afforded by this method permits selective removal of the clinically unpredictable cancerous outgrowths. The maximum conservation of normal tissues, including the cartilaginous framework that gives shape to the ear, is a benefit next in importance to the unusually high 5-year cure rates (97.1% in a series of 1213 cases of basal cell carcinoma and 92.3% in a series of 871 cases of squamous cell carcinoma). The fresh-tissue technique for removing most auricular carcinomas usually permits the excision of the successive layers in 1 day, and repair, if needed, can be done immediately. The fixed-tissue technique is still used by the authors for some extensive, bone-invading carcinomas.